tbuckley/cabot-search huggingface dataset:
Updated health-related quality of life of patients with TRK-fusion cancer treated with larotrectinib in clinical trials.
Authors: Shivaani Kummar, Lin Shen, Cornelis Martinus van Tilburg, Daniel S.W. Tan, Francois Doz, Raymond S. McDermott, C. Michel Zwaan, Karen N. Keating, Costel Chirila, Ricarda Norenberg, Marc Mardoche Fellous, Nicoletta Brega, Rui-hua Xu, Theodore Willis Laetsch, Alexander E. Drilon, David S. Hong
Journal: Journal of Clinical Oncology (2022)

6563 Background: NTRK gene fusions have been identified as oncogenic drivers in patients (pts) with TRK fusion cancer across multiple solid tumors. Larotrectinib, a highly selective, CNS-active TRK inhibitor has shown high response rates, durable disease control, and a favorable safety profile in pts with TRK fusion cancer and is approved in over 40 countries. Larotrectinib has demonstrated rapid health-related quality of life (HRQOL) improvement in a group of 57 adult and pediatric pts (Kummar et al, Curr Prob Canc 2021). Here, we report updated HRQOL results for larger group of pts treated with larotrectinib. Methods: HRQOL data were collected in two ongoing trials (NCT02576431, NCT02637687) of larotrectinib in pts with TRK-fusion cancer using the EORTC QLQ-C30, EQ-5D-5L questionnaires and were analyzed descriptively and longitudinally. Scores from the EORTC QLQ-C30 Global Health Status (GHS), EQ-5D-5L VAS range from 0 to 100, with higher scores indicating better QOL. We also calculated the proportion of pts with either below normal or normal and above normal HRQOL scores against values in the literature for the US general population. Results: By July 2021, 113 adults with TRK-fusion cancer had received larotrectinib and completed the baseline (BL) and ≥ 1 post-BL questionnaire. The majority of pts had clinically meaningful HRQOL improvements during treatment (Table). For EORTC QLQ-C30 GHS, most adults maintained or improved scores from BL at or above the normal population level category. HRQOL improvements (change from BL &gt; 0) occurred after ̃2 months of treatment in 75% of adults. Median duration of pts with sustained improvement in EORTC QLQ-C30 GHS, and EQ-5D-5L VASs was 12.5 months (range, 1.8-34.1), and 12.9 months (range, 1.8-34.0), respectively. HRQOL results were consistent across multiple data cuts. Conclusions: Patients with TRK-fusion cancer treated with larotrectinib continued to have rapid, clinically meaningful, and sustained improvements in HRQOL. Clinical trial information: NCT02576431, NCT02122913, NCT02637687.
Merkel polyoma virus specific T-cell receptor transgenic T-cell therapy in PD-1 inhibitor refractory Merkel cell carcinoma.
Authors: Joshua Veatch, Kelly Paulson, Yuta Asano, Lauren Martin, Bo Lee, Evan Thomas Hall, Shailender Bhatia, Paul Nghiem, Aude Chapuis
Journal: Journal of Clinical Oncology (2022)

9549 Background: Merkel cell carcinoma is an aggressive neuroendocrine tumor of skin origin with most cases caused by the Merkel polyoma virus (MCPyV). While many patients benefit from PD-1/PD-L1 axis blockade, most patients do not respond or develop resistance. We sought to ask whether adoptive transfer of autologous T cells transduced with MCPyV specific T cells could lead to clinical responses in PD-1 inhibitor refractory patients. Methods: Five MCPyV positive, HLA-A02 patients with PD-1 inhibitor refractory metastatic Merkel cell carcinoma were treated with adoptive transfer of CD62L+ CD8+ and CD4+ autologous T cells transduced with a T cell receptor (TCR) targeting an HLA-A0201 restricted MCPyV epitope. Two different strategies were used to facilitate T cell expansion: In 3 patients, single fraction radiation was administered to a subset of lesions prior to T cell transfer. In 2 patients, lymphodepleting chemotherapy with cyclophosphamide and fludarabine was administered prior to T cell transfer. Anti PD-1/PD-L1 therapy was given 14 days after T cell infusion. Transgenic T cells were visualized in tumor biopsies by multiplex immunohistochemistry. Results: 5 patients were treated, with 4 patients receiving 100 million tetramer positive CD8+ T cells and one patient receiving 500 million cells. 3 patients received second infusions with between 300 million and 900 million tetramer positive cells. No dose limiting toxicities or cytokine release syndrome were observed. T cell persistence was lower in the 2 patients treated with lymphodepleting chemotherapy relative to the 3 patients treated with single fraction radiation. Transgenic T cells persisted at tumor sites greater than 1 month following transfer. 4 patients experienced progressive disease, and a single patient had a mixed response and greater than 1 year disease free interval following local therapy of an isolated site of progression. The responding patient was the only patient with class I MHC staining on tumor cells prior to treatment, and the site of local progression in that patient showed the presence of TCR transgenic T cells but loss of class I MHC expression. Conclusions: MCPyV specific transgenic T cells are safe, traffic to tumor sites, and can result in a clinical response, but their clinical activity may be limited by down-regulation of class I MHC expression on tumors. A future trial will address strategies to increase class I MHC expression on Merkel tumors. Clinical trial information: NCT03747484.
Predicting hyperglycemia among patients receiving alpelisib plus fulvestrant for metastatic breast cancer.
Authors: Xuan Ge, Carolyn E. Behrendt, Susan Elaine Yost, Niki Patel, Raynald Samoa, Daphne B. Stewart, Mina S. Sedrak, Sayeh Moazami Lavasani, James Ross Waisman, Yuan Yuan, Joanne E. Mortimer
Journal: Journal of Clinical Oncology (2022)

1060 Background: Although hyperglycemia is recognized as a common adverse event (AE) on alpelisib (ALP), this AE has been little studied outside clinical trials. We report the frequency of ALP-associated hyperglycemia in a real-world setting and evaluate proposed risk factors. Methods: We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with ALP+fulvestrant (FUL) between August 2019 and December 2021. Five primary characteristics (diabetes, prediabetes, body mass index (BMI), age, Asian ancestry) were evaluated as independent risk factors for ALP-associated hyperglycemia using ordinal logistic regression that considered 3 glycemic levels: normoglycemia, grade 2, and grade 3-4 hyperglycemia. Overall risk of error from multiple hypothesis testing was kept below 5% using the False Discovery Rate method. Results: The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years, 13.0% with Asian ancestry. One third (33.7%) of patients had pre-existing diabetes, another 9.8% had pre-diabetes only. One third (32.6%) were obese, another third (31.5%) were overweight. Hypertension and hyperlipidemia were present in 53.3% and 41.3%, respectively. On ALP+FUL, 59 (64.1%) current subjects developed hyperglycemia of grade 1-4, a rate no different than the 181/284 (63.7%) reported in the ALP+FUL arm of the SOLAR-1 trial. Among our subjects, risk of grade 2-4 hyperglycemia was independently increased by 4 of 5 hypothesized risk factors, specifically pre-existing diabetes (Odds Ratio 3.75, 95% Confidence Interval: 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), each unit of BMI above 20 (1.17, 1.07-1.28), but not by additional year of age (1.01, 0.97-1.05). Exploratory analysis detected no association with pre-existing hypertension or hyperlipidemia. Conclusions: These findings suggest that Asian ancestry merits further study as a predisposing factor for ALP-associated hyperglycemia. Our study of this AE also demonstrates that pre-existing hyperglycemia and greater BMI are independent risk factors; diabetes and pre-diabetes confer similar degrees of risk; risk from BMI begins after BMI 20 and rises incrementally; and age is not a contributing factor.
Accuracy of SelectMDx compared to mpMRI in the diagnosis of prostate cancer: A diagnostic meta-analysis
Authors: R. Sari Motlagh, T. Yanagisawa, T. Kawada, E. Laukhtina, P. Rajwa, A. Aydh, F. König, M. Pallauf, N. Huebner, P. Baltzer, P. Karakiewicz, A. Heidenreich, S. Shariat
Journal: European Urology (2022)
Mental health care for oncology patients in community settings.
Authors: Danielle Gentile, Andrew J. Klink, Yolaine Jeune-Smith, Ajeet Gajra, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2022)

e18525 Background: Research suggests that between thirty and fifty percent of patients with cancer experience psychiatric disorders across the cancer trajectory. As part of standard cancer care, mental health care can reduce distress and psychological morbidity for patients and improve their quality of life. Mental health treatment may even improve cancer survival rates. Considering the mental health issues relevant to cancer, implementation of mental health care into routine clinical care remains a challenge among community-based hematologists/oncologists (cH/O). Methods: Practicing U.S. cH/O completed a cross-sectional, web-based survey from September through November 2021. The survey collected demographic information and assessed physicians’ experiences and awareness regarding mental health diagnosis, frequency, severity, and management among their patients. Data were summarized using descriptive statistics. Results: Participants (N = 243) specialized in hematology/oncology (63%), medical oncology (36%) (1% other). The majority practiced in community-based settings unaffiliated with an academic center or hospital (73%). The majority (92%) agreed that mental health can significantly impact the health outcomes of patients with cancer. The majority (80%) frequently see patients coping with mental illness or distress. More than a quarter of the participants reported that their practice has clinical psychologists (27%), and nearly half (46%) have social workers on staff. About half (51%) occasionally refer patients for mental health services/treatment while 15% rarely or never refer. Nearly half (49%) indicated they do not have adequate resources to support the mental health needs of their patients with cancer. Conclusions: Our findings that oncologists have high levels of awareness about mental health issues among their patients with cancer is encouraging as is their incorporation of professionals on the care team to address this need. However, oncologists indicated that their available mental health resources are inadequate to meet patients’ needs and external referrals are limited. These findings suggest that additional resources and referrals are needed to ensure that patients will consistently receive the mental health care they need. Future research to assess the impact of mental health care on clinical outcomes including quality of life in patients with cancer is warranted.
Disparities in biomarker testing in ovarian cancer.
Authors: Anna Jo Bodurtha Smith, Rafael Alvarez, Jonathan Heintz, Ashley Ford Haggerty, Emily Meichun Ko
Journal: Journal of Clinical Oncology (2022)

e18596 Background: Biomarker-based treatments have revolutionized treatment in ovarian cancer. Our objective was to examine the association of biomarker testing in ovarian cancer with patient and health system factors. Methods: We conducted a retrospective cohort study of ovarian cancer patients diagnosed from 2011-2021using the nationwide de-identified, electronic health record-derived Flatiron Health database. We used multi-level regression modeling to analyze the association of patient, sociodemographic, health system, and cancer factors with receipt of biomarker testing. We analyzed results overall and by biomarker: BRCA, homologous recombination deficiency (HRD) or genomic instability score (GIS). Results: Of 8,519 patients with ovarian cancer, 55.4% (95%CI 54.3-56.4) had undergone any biomarker testing. 55.3% (95%CI 54.3-56.5) had undergone BRCA testing and 6.1% HRD/GIS (95%CI 5.6-6.6). Medicare insurance, older age, ECOG of 2+, and living in Puerto Rico was associated with lower likelihood of biomarker testing, while recurrence or a later year of diagnosis was associated with greater likelihood of biomarker testing. Findings were similar for BRCA and HRD/GIS. Conclusions: Only 55% of patients underwent biomarker testing. Insurance type, ECOG status, region, and recurrence were predictors of ever undergoing biomarker testing. Interventions to improve Medicare coverage and care of medically complex patients may improve biomarker testing and use of directed therapies in ovarian cancer.[Table: see text]
Adrenalectomy for metastasis: The impact of primary histology on survival outcome
Authors: M. Ferriero, A.M. Bove, G. Tuderti, U. Anceschi, L. Misuraca, A. Brassetti, R. Mastroianni, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2022)
Using cell-free circulating tumor DNA (cfDNA) to identify guideline-relevant biomarkers for therapy selection in 14,000 patients (pts) with metastatic colorectal cancer (mCRC).
Authors: Pashtoon Murtaza Kasi, Benjamin R. Tan, Timmy Q. Nguyen, Jason S. Starr, Leslie A. Bucheit, Leylah Drusbosky, Caroline Weipert
Journal: Journal of Clinical Oncology (2022)

3601 Background: Two cfDNA assays are FDA-approved for use in advanced cancer pts across solid tumors. While several NCCN guidelines recommend cfDNA as a valid and useful method for molecular testing, the utility varies by cancer type. Despite the growing number of molecular alterations pertinent to first-line treatment in mCRC, current guidelines offer little guidance on the use of cfDNA in mCRC. Here we assess the ability of cfDNA to detect guideline-relevant actionable biomarkers informative for first-line therapy selection and beyond in patients with mCRC. Methods: We queried consecutive samples from advanced cancer pts with a diagnosis of CRC who underwent testing via a commercially available cfDNA assay (Guardant360) from September 2018 to January 2022. Validation and content of this assay has been previously described. To enrich for less heavily treated pts, we limited analysis to those whose first cfDNA test was done during the study period and only included the pt’s first test. The maximum variant allele fraction (maxVAF) for each test was used as a proxy for tumor shed and was compared between cancers with a Mann-Whitney test. The frequency of suspected germline alterations was assessed only in pts who received testing via a panel version with expanded mismatch repair (MMR) gene coverage. Tissue frequencies for select biomarkers were obtained from the MSK-IMPACT Clinical Sequencing Cohort in cBioPortal. Results: In total, 14,345 pts with mCRC received their first cfDNA test during the study period, with 92% of pts (13,190) having &gt;1 cfDNA alteration detected. Median age was 62 and 44% of pts were female. The frequencies of key biomarkers are listed in Table 1. The median maxVAF was 5.6%, compared to 2.5% and 1.8% for pts with advanced gastric and NSCLC, respectively (p = &lt; 0.0001 for both). The average turnaround time (TAT) for tests was 7 calendar days. Conclusions: cfDNA results from pts with mCRC demonstrated detection of biomarkers essential to first-line treatment decisions at a frequency comparable to what has been reported via tissue genotyping. mCRC pts had significantly higher tumor shed compared to other cancer types with guidelines that recommend cfDNA as an option for molecular testing, suggesting a potential gap in coverage. Tissue availability in mCRC does not guarantee comprehensive testing is completed quickly (compared to the 7-day TAT seen for cfDNA here), making it an attractive alternative strategy for first-line therapy selection in mCRC. [Table: see text]
SURG-01. The Tentative Application of En Bloc concept in the Pediatric Brain Tumor: A Retrospective Study of 171 Cases from A Large Pediatric Center in China
Authors: Liangliang Cao, Shuaiwei Tian, Yang Zhao, Baocheng Wang, Jiajia Wang, Jie Ma
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The less allowable blood loss and tolerance of intraoperative blood loss of children lead to the high rate of massive blood transfusion. The surgical concepts of en bloc resection may contribute to the improvement of brain tumor resection. OBJECTIVE: To investigate the effects of en bloc concept on short outcomes of pediatric brain tumors and factors associated with the application of en bloc concept. METHODS: According to the surgical concept involved, the patients were divided into three subgroups-complete en bloc concept, partial en bloc concept and piecemeal concept. The matching-comparison(en bloc group consisting of the first two subgroups and piecemeal group) was conducted to investigate the effect of the en bloc concept on the short-term outcomes. Then the patient data after January 2018, when the en bloc concept was routinely integrated into brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept. RESULTS: In the en bloc group, the perioperative outcomes, including hospital stay(p=0.001), PICU stay(p=0.003), total blood loss(p=0.015), transfusion rate(p=0.005) and complication rate(p=0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume, bottom vessel, and imaging features, like encasing nerve or pass-by vessel, finger-like attachment, ratio of “limited line” and ratio of “clear line” remained independent predictors for the application of en bloc concept in our medical center. CONCLUSION: The application of en bloc concept based on the imaging features can improve the short-term outcomes.
The 10-year journey of non–small cell lung cancer: A real-world experience.
Authors: Hyun Ae Jung, Kyunga Kim, Sang Ah Chi, Hyeyeon Yu, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2022)

9133 Background: Over the past 10 years, the treatment of non-small cell lung cancer (NSCLC) has been continuously revolutionized. This study evaluated how this revolution improved outcomes in the real-world. Methods: We collected clinical, pathological, and molecular data of patient with NSCLC using an in house real-time updated cohort (ROOT-HEALTH). The primary objective was the 3-year survival (OS3) rate by clinical stage, histology, and driver mutations including EGFR, ALK, ROS1, RET, MET exon 14 skipping, BRAF V600E, KRAS G12C, and NTRK between two time periods (Period I: 2010-2015 vs. Period II: 2016-2021). Results: We included data on 22,060 patients who received any anti-cancer treatment between January 2010 and December 2020. Adenocarcinoma (AD) was the predominant histology (70.2% in Period I vs. 74.2% in Period II) (Standardized mean difference [SMD] = 0.09, P &lt; 0.001). In Period I, 36.8%, 10.4%, 15.9%, and 34.6% patients were in stage I, II, III, and IV respectively. In Period II, 44.8%, 9.6%, 15.1%, 29.9% were in each stage, respectively (SMD = 0.15, P &lt; 0.001). Patients during Period II were more likely to perform molecular tests for EGFR, ALK, and/or others than those during Period I in both of AD (79.1% in Period I vs. 95.1% in Period II) and non-AD (53.5% in Period I and 85.0% in Period II). In patients with AD, 49.4% in Period I and 56.4% in Period II had any druggable mutations. Among non-AD patients, 4.9% and 6.2% of patients had any druggable mutations in Period I and II, respectively. In patients with AD, in Period I, the OS3 rates were 92.9 %, 72.6%, 56.6%, and 29.0% for each stage (I, II, III, and IV), respectively. In Period II, the OS3 rates of AD were 96.4 %, 86.8%, 70.2%, and 52.1% for each stage, respectively (P &lt; 0.001). In stage IV AD with EGFR mutation, the OS3 rates were 42.5% and 65.4% in Period I and II, respectively (P &lt; 0.001). In stage IV AD with ALK rearrangement, the OS3 rates were 53.2% and 73.6% in Period I and II, respectively (P &lt; 0.001). In patients with non-AD, the OS3 rates were 71.6%, 60.2%, 38.8%, and 10.2% for each stage in Period I. In Period II, the OS3 rates of non-AD were 83.1%, 73.7%, 58.2%, and 29.6% for each stage (P &lt; 0.001). In stage IV non-AD with any druggable mutations, the OS3 rates were 27.1% and 46.0% in Period I and II, respectively (P = 0.05). Conclusions: Our study is meaningful as a large-scale study that reflects changes of survival outcome in a timely manner.Through our real-world experience of over 10 years, the proportions of early stage and were found to be increased. The implementation of molecular testing has also been expanded. Of note, the survival outcomes were remarkably improved across all stages, especially in patients with stage III-IV. Further improvement of outcomes through effect of emerging driver mutations in the next five years is expected.
Use of Moses 2.0 with extended frequency and optimized Moses vs. high power laser in MiniPCNL: Interim analysis of a randomized controlled trial
Authors: E. Emiliani, A.K. Kanashiro, S. Fontanet, J. Aumatell, J.F. Calderón-Cortez, I. Sanz, J.D. Iregui-Parra, F. Sanchez-Martin, F. Millan, O. Angerri-Feu
Journal: European Urology (2022)
En-bloc versus conventional transurethral resection of bladder tumors: Single-center prospective randomized trial
Authors: A. Gallioli, P. Diana, M. Fontana, A. Territo, A. Piana, F. Algaba, Ó. Rodriguez-Faba, A. Mercade, A. Bravo, A. Rosales, J.M. Gaya, J. Palou, A. Breda
Journal: European Urology (2022)
Understanding the relationship between gliomas and T cells: Paving the way for effective immunotherapy
Authors: Catalina Lee-Chang
Journal: Neuro-Oncology (2022)

Journal Article Understanding the relationship between gliomas and T cells: Paving the way for effective immunotherapy Get access Catalina Lee-Chang Catalina Lee-Chang Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USAThe Malnati Brain Tumor Institute, Chicago, Illinois, USA Corresponding Author: Catalina Lee-Chang, PhD, Simpson and Querrey Biomedical Research Center, Suite SQ6-405, 303 E Superior St, Chicago, IL 60611, USA (catalina.leechang@northwestern.edu). https://orcid.org/0000-0002-7675-2124 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 10, October 2022, Pages 1658–1659, https://doi.org/10.1093/neuonc/noac152 Published: 06 June 2022 Article history Published: 06 June 2022 Corrected and typeset: 08 July 2022